Conflict of Interest -primary prevention and secondary fracture prevention for the Advanced Practice Nurse Anne Lake, DNP, ONP-C, FNP-C, CCD I hereby certify that, to the best of my knowledge, no aspect of my current personal or professional situation might reasonably be expected to affect significantly my views on the subject on which I am presenting other than the following: Disclosures: Consultant/Advisory Board National Foundation National Bone Health Alliance Eli Lilly Learner Outcome As a result of this learning activity, the participant will gain confidence and apply knowledge and skills toward Primary Prevention and Secondary Fracture Prevention to the patient at risk for Low Bone Mass or with a diagnosis of Objectives 1. Review current definition of : Epidemiology, Diagnosis and primary prevention versus secondary fracture prevention 2. Describe relevant clinical history and physical findings to identify patients at risk for fracture 3. Recognize causes of secondary osteoporosis and when laboratory testing is appropriate 4. Explore non-pharmacologic preventive measures 5. List the available medications for osteoporosis and potential side effects : Quick Review Postmenopausal - Imbalance in remodeling favoring resorption over formation-new LOSS Aging-related bone loss-defective osteoblastic function, stem cell exhaustion/depletion, failure of osteoclast to cross-talk with osteoblast (failure of communication) due to reduced growth factor matrix. 1
Definition of Continues to evolve Not just based on BMD readings can be diagnosed in presence of fragility fracture Fragility Fracture: a fragility fracture is any fracture that occurs from a fall from standing height or less or if someone lifts something of light weight (usually 5-10 pounds or less) and sustains fracture Definition: NIH Consensus Conference A skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture Bone strength = Bone Quantity (BMD) + Bone Quality (micro-architecture, etc) 1 Normal 1 NIH Consensus Conference, 2000. 2 Source: Dempster DW, et al. J Bone Miner Res. 1986:1:15-21 Reprinted with permission from the American Society of Bone and Mineral Research Evaluating Bone Strength Bone strength primarily reflects the integration of BMD and bone quality 1 Bone Strength BMD and = Bone Quality Obtain Through a DXA Test Bone Characteristics 1 1. Rate of bone remodeling 2. Architecture 3. Degree of mineralization 4. Damage accumulation Clinical Indicators 1. Increasing age 2 2. Previous fragility fractures 3 BMD=bone mineral density. DXA=dual-energy x-ray absorptiometry. 1. NIH. JAMA. 2001;285(6):785-795. 2. Rehman MT, et al. J Clin Pathol. 1994;47(6):529-534.3. Genant HK, et al. Int. 2007;18(1):69-76. Bone type/cell Type Cortical Bone: turns over slowly and mineralization takes about 130 days Trabecular Bone: turns over quickly and mineralization takes about 30 days Osteoclast: Bone Turnover = Resorption Osteoblast: Bone Formation= Formation Diagnosis of Osteopenia or by BMD Osteopenia Bone density T-scorein wrist, hip or spine is between -1.1 to -2.4 Special Group: In a premenopausal female, perimenopausalfemale and male under the age of 50 use the Z score. Not a T score. If less than -2.0 do not use the term osteoporosis Bone density T score in wrist, hip or spine is -2.5 or lower Special Group: In a premenopausal female, perimenopausalfemalor male under the age of 50 and a Z score of -2.0 must state Bone Mass is lower than expected for this age group. 2
FRAX tool Fragility Fracture Stats Use in Osteopenia Use of the FRAX(fracture risk assessment tool) is important in someone with osteopenia to determine if treatment is indicated. If FRAX for major osteoporotic fracture is 20% or higher or risk for hip is 3% or higher (high risk for fracture in the next 10 years) www.shef.ac.uk/frax FRAX not reliable if patient is on treatment or has been treated in the past. Fragility fractures are an epidemic in the US with over 2 million occurring each year 54 million now affected by osteoporosis or low bone mass 1:2 females and 1:4 males 50 and older will have an osteoporotic fracture in their lifetime More hospitalization cost associated with osteoporotic fracture admissions/care than heart attacks, strokes and breast cancer. Prevalence of and and Low Low Bone Bone Mass Mass Americans Age 50 and Above Affected by /Low Bone Mass, 2010 to 2030 (projected) 17% of the ENTIRE U.S. POPULATION (2010) 80 70 60 50 40 30 20 54 million of 99 million Americans age 50+ (2010) 10 Millions 0 2010 2030 Wright NC, et al. JBMR doi:10.1002/jbmr2269 +27% change from 2010 to 2030 Low Bone Mass Question 1 What is the cell type responsible for bone resorption? a. White Blood Cell b. Osteoblast c. Osteoclast d. Red Blood Cell The Impact of and Fractures ½ of women and ¼ of men over age 50 will break a bone due to osteoporosis 26% of women refracture within 1 year after a vertebral fracture Hospitalization Burden for Osteoporotic Fractures and Other Serious Diseases in Older US Women Figure 1. Percent of hospitalizations* for osteoporotic fractures and other serious diseases combined, 2000 2011 Cast Mountain represents just 1 DAY of fractures caused by osteoporosis in the U.S. Lindsay Lindsay R et R al. et OsteoporosInt. al. OsteoporosInt. 2005;16:78-85. 2005;16:78-85. Wright Wright NC, et NC, al. et JBMR al. JBMR doi:10.1002/jbmr2269 doi:10.1002/jbmr2269 *Principal diagnosis codes were used to define the outcomes. Singer AJ, et al. International. 25(4) suppl:503-522;2014. Singer AJ, et al. Mayo Clinic Proceedings 2015 90, 53-62 Used by permission from NBHA and Dr. Andrea Singer 2016 3
Figure2 Average Length of Stay and Cost per Hospitalization for Osteoporotic Fracture and Other Serious Diseases Total population cost for hospitalization per year for the 2000-2011 time period: $5.1 billion for osteoporotic fractures $4.3 billion for MI $3.0 billion for stroke $0.5 billion for breast cancer. The Impact of and Fractures Every year, of 300,000 hip fracture patients 20%-25% of patients die (greater risk of dying persists for at least 5 years) 25% end up in nursing homes 50% never regain previous function Half of hip fracture patients give advance notice an obvious opportunity for prevention 50% of patients with a hip fracture had a prior osteoporotic fracture Singer AJ, et al. Mayo Clinic Proceedings 2015 90, 53-62 Wright NC, et al. JBMR doi:10.1002/jbmr2269 Burge RT, et al. JBMR. 22(3):465 475,2007. Adapted from NOF. Clinician s Guide to Prevention and Treatment of. 2013 and US Department of Health and Human Services. Bone Health and : a Report of the Surgeon General. Rockville, MD. 2004. National Gap in Care Numerous studies show a failure to diagnose and treat osteoporosis, even in patients who have sustained a fracture The gap between what is known about bone health and the application of that knowledge to patient care remains large 2003 NCQA HEDIS Data Myocardial Infarction Breast cancer screening Colorectal cancer screening Osteoporotic fracture 93% receive beta blockers 74% of eligible patients 50% of eligible patients 18% receive osteoporosis management (DXA and/or prescription medication) Question 2 What percent of patients presenting with a hip fracture had already had a previous fragility fracture? a. 25% b. 38% c. 15% d. 50% 2003 First year osteoporosis included in measures US Dept of Health and Human Services. Bone Health and : A Report of the Surgeon General. Rockville, MD,2004 Primary Prevention of Health History clues for possible Postmenopausal/ Early menopause or Hypogonadism Medical Conditions known to be associated with bone loss Medications known to be associated with compromised bone strength Family History of Reported height loss since age 20 BMD shows osteopenia Hx of gastric bypass Secondary Fracture Prevention Known factors in Health History: clues indicating History of Fragility fracture of spine, wrist, or spine but must consider other areas as well Medical Conditions known to be associated with bone loss Medications known to be associated with compromised bone strength Family History of Reported height loss since age 20 4
Clinical Risk Factors for Low Bone Mass Loss of height Low body weight Advanced age Late age at menarche Menopausal Time since menopause Smoking Dietary calcium Alcohol intake Medications Inflammatory diseases Prior fragility Risk factors for Osteoporotic Fracture Low BMD Advancing age Prior fragility fracture Family history of osteoporosis or fragility fracture in a first degree relative (genetics) Current smoker Low body weight Falls Sarcopenia Dementia Riggs BL. NEJM. 1986;314:1676. RibotC. Clin Endocrinol. 1992;36:225 Marshall D et al. BMJ. 1996; 312:1254. Hui SL et al. J ClinInvest. 1988; 81:1804. Clinical Risk factors are poor indicators for Low Bone Density Review of 9 studies Risk factors accounted for 15-43% of the variability in spine BMD BMD cannot be predicted from clinical risk factors Age and weight accounted for the greatest proportion of the observed variance Conclusion: Clinical risk factors are not a substitute for BMD testing Ribotet al. Am J Med. 1995;98 (suppl2a), 52S-5 Clinical Presentation indicating increased fracture risk Impaired ambulation Muscle weakness Impaired balance Reduced vision Macular Degeneration Glaucoma Bifocals Orthostatic hypotension Physical Findings Clinical presentation indicating signs of prior fractures Loss of height (usually 1.5 inch height loss since age 20 (NOF recommends annual height measurement with a stadiometer Kyphosis Chest deformity Protuberant abdomen Rib-pelvis overlap Question 3 What is not a clinical risk factor for low bone mass? a. reported history of height loss since age 20 b. Diabetes type 1 and 2 c. Low BMI d. male pattern baldness Causes of Secondary Endocrine Disorders affecting bone metabolism Hypercalciuriawith or without renal stones Hypogonadism (incl. hyperprolactinemia) Hyperparathyroidism Hyperthyroidism Cushing's syndrome Diabetes (types 1 and 2) Acromegaly (via hypogonadism) Osteogenesis Imperfecta P. Tannirandorn Osteoporos Int. 2000;11:637 5
Causes of Secondary Secondary Causes of Drugs affecting bone quality GI Tract Disorders Bone Marrow Based Disorders Excess glucocorticoids Excess thyroid hormones Anticoagulants (heparin) GnRH agonists Anticonvulsants Aromatase inhibitors Thiazolidinediones Opiates P. Tannirandorn Osteoporos Int. 2000;11:637 Cyclosporine Chemotherapy Alcohol Loop diuretics PPI long term use Gastrectomy Inflammatory bowel disease Celiac disease Intestinal bypass surgery Primary biliary cirrhosis Pancreatic insufficiency Hepatitis B, C Multiple myeloma Hemolytic anemia, hemoglobinopathies Myelo-and lymphoproliferative disorders Skeletal metastases (diffuse or localized) Gaucher sdisease Mastocytosis Inflammatory Disorders Secondary Causes of RA SLE Ankylosing spondylitis Polymyalgia Rheumatica Vasculitis Other Immobilization AIDS/HIV Organ transplantation COPD Anorexia Malignancy Vitamin D Insufficiency and Deficiency Lack of sun exposure and dietary vitamin D Age-related decline in cutaneous production Gastrointestinal disease Liver disease Renal disease Drugs (phenytoin, phenobarbital) Holick, MF, NEJM; 2007 357:266-281 When to consider further workup in certain patients Men with osteoporosis Unexplained fracture Unexpected low BMD Poor response to therapy Clinical suspicion of secondary causes in any patient with osteoporosis Adopted from International Society of Clinical Densitometry(ISCD) recommendations Labs to consider in Secondary Evaluation CBC Chemistries (Ca, Creat, PO4, Mg) Liver function test TSH Vitamin D 25(OH)D PTH Total testosterone and gonadotropins in younger men 24 hour urine calcium Consider in selected patients: SPEP, serum free light chains, UPEP, tissue transglutaminase, ferritin, homocysteine, tryptase, urinary free cortisol, urinary histamine Cosman, F 2014 NOF Clinicians Guide; www.nof.org 6
Question 4 When should you consider further workup in certain patients with osteoporosis to look for secondary causes? a. worsening BMD indicating poor response to therapy b. unexplained fracture c. unexpected low BMD d. clinical suspicion of secondary causes in any patient with osteoporosis e. All of the above Covered BMD Services Estrogen deficient women at clinical risk for osteoporosis Individuals with vertebral abnormalities on x-rays Individuals receiving long-term glucocorticoid therapy Individuals with primary hyperparathyroidism Individuals being monitored on osteoporosis therapy Check with your regional CMS carrier to determine the appropriate ICD-10 codes for use in your area! Refer bone density coverage on CMS website for your area Not all Fractures are due to : Indications for other imaging Consider bone scan or MRI if: Fracture is equivocal Fracture is remote Kyphoplasty/vertebroplastybeing considered Consider MRI or biopsy if: Concern of metastatic carcinoma Consider MRI if: Concern of lateral or posterior displacement Secondary Fracture Prevention: Reasons for Fragility Fracture treatment gap No recognition by orthopaedic surgeon/provider No diagnostic tests for factors contributing to skeletal fragility No DXA since recent fractures No calcium, vitamin D, or medications to reduce fracture risk No attention to reducing fall risk 7. Miller, A, Lake, A et. al. J Bone Joint Surg Am. 2015;97:675-81 d http://dx.doi.org/10.2106/jbjs.n.00957 Adopted from ISCD recommendations Wrist Hip Common areas of Fragility Fractures Spine New Clinical Position statement by the National Foundation to include other areas to be considered such as pelvic insufficiency fractures, humerus fractures, ankle fracture Highlight on Vertebral Fractures Most common fracture type Often silent Can be progressive Associated with Deformity, height loss, back pain Impaired breathing Increased morbidity and mortality Predict future spine and hip fractures 7
Highlight on Vertebral Fractures Important to detect because they: foretell future fracture risk evidence shows associated with increased mortality and morbidity (reduced quality of life) Often missed in the course of routine medical care (chest xraysand spinal films) Can be prevented with appropriate therapy Traditionally require X-ray for diagnosis X-ray is usually not obtained Possible solution: VFA can diagnose fracture at the time of DXA BMD measurement Question 5 Vertebral fractures are important to detect because they are a known predictor of future fractures a. True b. False Limitations on performing Central DXA Contraindicated Pregnancy Reasons to postpone Recent contrast study (generally less than 72 hours) - Spine measurement only Recent nuclear medicine scan (may be manufacturer specific) Reasons not to perform or inability to perform: Extensive orthopedic instrumentation Body weight greater than table limit Solution: Measure the forearm Treatment Goals in management Improve bone strength by improving bone mass Improve bone quality/possibly microarchitecture Reduce risk of future fractures If we could accomplish all of these we would have cure : Currently not possible Non pharmologicalpreventative modalities Weight Bearing exercises Resistance exercises Calcium Citrate/Carbonate 1000-1200mg daily with food, should partially come from dietary intake if possible Vitamin D3 1000-2000 units daily or more depending on patient s level Falls prevention, Core strengthening and Balance FDA approved Drugs Drugs PMO GIO Men Prevention/Treatment Prevention/Treatment Estrogen yes Baezdoxifene/CEE yes Calcitonin yes Alendronate yes yes yes yes Risedronate yes yes yes yes yes Ibandronate yes yes Zolendronic Acid yes yes yes yes Raloxifene yes yes Denosumab yes yes Teriparatide yes yes yes 8
Drug Classes: Estrogen Antiresorptives Slow/suppress osteoclastic activity Includes estrogen, estrogen receptor modulators, bisphosphonates, rank ligand inhibitor, calcitonin Anabolic Stimulates osteoblastic and osteoclastic activity Please note the osteoclastic activity levels off as osteoblastic activity continues to increase Includes teriparatide Class: antiresorptive BMD: increases at spine and hip Fractures risk reduction seen in vertebral and nonvertebral Extraskeletal: increases risk of breast cancer, reduces hot flashes, increases VTE risk, stimulates the endometrium, other Global Consensus Statement on Menopausal Hormone Therapy MHT is effective and appropriate for the prevention of osteoporosis-related fractures in at-risk women before age 60 years or within 10 years after menopause. Randomized clinical trials and observational data as well as meta-analyses provide evidence that standard-dose estrogenalone MHT -may decrease coronary heart disease and all cause mortality in women younger than 60 years and within 10 years of menopause. Note: Estrogen use for osteoporosis treatment would be off label 8. De Villiers, et. al., Climacteric, 2013; 16: 203-20 Bazedoxifene/Conjugated Estrogen Class: antiresorptive, selective estrogen receptor modulator plus estrogen BMD: prevents bone loss in early postmenopausal women Fractures: reduces risk of vertebral fractures (~40%), no proven benefit for hip or nonvertebralfractures Extraskeletal: reduces hot flashes, improves vulvovaginal atrophy Increases VTE risk, leg cramps, does not stimulate endometrium Silverman SL et al. J Bone Miner Res 2008;23(12):1923-34 Siverman SL et al. Osteoporos Int 2012;23(1):351-63 Kagan R et al. J Women s Health 2012;975-81 Raloxifene Class: antiresorptive, selective estrogen receptor modulator BMD: increases at spine and hip Fractures: reduces risk of vertebral fractures, no proven benefit for hip or nonvertebralfractures Extraskeletal: reduces risk of breast cancer, does not reduce hot flashes, VTE risk (similar to Estrogen and Tamoxifen) leg cramps, does not stimulate endometrium Other Benefits: favorable effect lipid profile, has no effect on risk of coronary events Bisphosphonates: Alendronate, Risedronate, Ibandronate and Zoledronic Acid Class: antiresorptive BMD: increases BMD at various skeletal sites Fractures: reduces risk of fractures Extra-skeletal considerations Specific dosing requirements for oral bisphosphonates Interval and IV/oral dosing available Occasional GI irritation Infrequent musculoskeletal pain Very rare -hypocalcemia, osteonecrosis of jaw, atypical femoral fracture Effect on bone resorption persists after discontinuation Unique to bisphosphonates 9
Things to consider with Bisphosphonate treatment Safety Concerns GI intolerance with the oral treatments Esophageal cancer (reported concern) Hypocalcemia (may be transient effect up to 10 days after subq injection) Atrial Fibrillation (reported concern) Renal Toxicity (reported concern) Check calcium and creatinine prior to treatment Flu like symptoms (myalgia, arthralgia, fever) 12-48 hours after IV infusion last usually 1-2 days sometimes up to a week Ocular effects Osteonecrosis of the jaw Atypical fractures (reported concern) Calcitonin Class: antiresorptive, biologic agent BMD: slight increase Fractures: reduces risk of vertebral fractures (around 30%) no proven benefit for hip or nonvertebral fractures Extra-skeletal considerations Possible analgesic effect Occasional nasal irritation, rarely epistaxis No known drug interactions Calcitonin Package Insert Updated 3/2014 Calcitonin indications include treatment of postmenopausal osteoporosis when alternative treatments are not suitable Fracture reduction efficacy has not been demonstrated Due to the possible association between malignancy and calcitonin-salmon use, the need for continued therapy should be re-evaluated on a periodic basis Denosumab Class: antiresorptive, fully human monoclonal antibody, binds and inhibits RANKL BMD: increased at spine and hip Fracture: reduces spine, hip and nonvertebralfractures Extra-skeletal considerations SQ injection every 6 months Hypocalcemia, infection, ONJ, AFF and rash possible Calcitonin prescribing information: Revised 03/2014 Teriparatide: rhpth(1-34) Class: anabolic, hormone BMD: increases at spine and hip Bone turnover markers: increased Fractures: decreases at spine and nonvertebral, study too small to demonstrate hip fracture benefit Extra-skeletal considerations: Osteosarcoma in rats, daily subcutaneous injection, refrigeration, hypercalcemia, leg cramps, dizziness, high cost, limit of 2 years of therapy Changes in Cortical Geometry and Trabecular Architecture with PTH Treatment That Result in Anti-fracture Efficacy Intermittent PTH is Anabolic BUT continuous PTH is Catabolic Bone volume improves Periosteal diameter increases Cortical thickness increases Porosity (near endocortical surface increases) Endocorticaldiameter decrease Bone volume increases Trabecular thickness increases Connectivity increases 10
Strontium Ranelate Question 6 Class: strontium is a mineral that binds to bone Bone turnover markers: Decreases resorption, possibly increases formation (uncouples?) BMD: increases at spine and hip NOTE: part of increased BMD is due to deposition of strontium (higher atomic weight than calcium) in bone, relation to increased bone strength not clear Fracture: decreases spine and nonvertebral fractures AEs: possible CV risk, diarrhea, rash including StevensJohnson syndrome Available as a prescription in Europe (Strontium Ranelate) Not available in the US, but OTC strontium preparations (not strontium ranelate) are available Unknown if these preparations have beneficial skeletal effects Treatment goals for low bone mass with high fracture risk and osteoporosis include all of the following? a. Improve bone strength by improved bone mass b. Improve bone quality/possibly microarchitecture c. Reduce risk of future fractures d. All of the above Treatment summary: New Drugs on the Horizon 1. Two options for treatment: several antiresorptives and one anabolic 2. Estrogen reduces vertebral and non-vertebral fractures, but is approved only for osteoporosis prevention, not treatment 3. Raloxifenehas skeletal effects generally similar to those of estrogen but only reduces vertebral fracture risk 4. Bisphosphonates reduce fracture risk for vertebral and nonvertebral fractures 5. Denosumab increases bone mass, decreases bone resorption and reduces vertebral and non-vertebral fracture risk 6. Anabolic treatment induces significant increases in bone mass and decreases vertebral and non-vertebral fracture risk Antiresorptive: Cathepsin K Inhibition: Odanacatib Decreases bone resorption, increase in periosteal bone formation, increased cortical volumetric BMD Osteoanabolics Abaloparatide PTHrP(1-36)» Transdermal route, weekly administration, chip technology Combination Therapy: Antiresorptive and osteoanabolic agent A pure osteoanabolic therapy: Sclerostin Antibody Therapy Fracture Liaison Service (FLS) Model of Care A coordinatedpreventive care model which operates under the supervision of bone health specialists and collaborates with the patient s primary care physician FLS programs coordinate post-fracture care through an FLS coordinator(generally a nurse, NP, or PA) Patients with recent fractures are tracked via a population registry Processes and timelines established for patient assessment and follow-up FLS programs Recognize that patients who have fractured are at highest risk of future fractures Have greatly reduced the number of fractures and have achieved cost savings by identifying and appropriately treating post-fracture patients Miller, A, Lake, A et. al. J Bone Joint SurgAm. 2015;97:675-81 d http://dx.doi.org/10.2106/jbjs.n.00957 1.Riggs BL. NEJM. 1986;314:1676. Ribot C. Clin Endocrinol. 1992;36:225 2. Marshall D et al. BMJ. 1996; 312:1254. Hui SL et al. J ClinInvest. 1988; 81:1804. NOF Clinician s Guide. 2013 www.nof.org Lang, et. al. Bone. 2008; 42:798-805 3. Ribotet al. Am J Med. 1995;98 (suppl 2A), 52S-55 4. P. Tannirandorn Osteoporos Int. 2000;11:637 5. Holick, MF, NEJM; 2007 357:266-281 6. Cosman, F 2014 NOF Clinicians Guide; www.nof.org 7. Miller, A, Lake, A et. al. J Bone Joint Surg Am. 2015;97:675-81 d http://dx.doi.org/10.2106/jbjs.n.00957 8. De Villiers, et. al., Climacteric, 2013; 16: 203-20 9. Silverman SL et al. J Bone Miner Res 2008;23(12):1923-34 Siverman SL et al. Osteoporos Int 2012;23(1):351-63 Kagan R et al. J Women s Health 2012;975-81 11